Determination and verification of reference interval limits in clinical chemistry. Recommendations for laboratories on behalf of the Working Group Guide Limits of the DGKL with respect to ISO Standard 15189 and the Guideline of the German Medical Association on Quality Assurance in Medical Laboratory Examinations (Rili-BAEK)

Abstract Laboratory measurement values require interpretative assistance e.g. so-called guide limits (GL), as an interpretative aid. Legal and normative requirements for medical laboratories do not provide specific information for their implementation and verification. A German Society for Clinical Chemistry and Laboratory Medicine (DGKL) Working Group GL (WG-GL) has, therefore, developed recommendations to support medical laboratories in the management of GL. A specific objective was to create a framework that mainly takes into account those aspects that can be realistically implemented by routine laboratories and that should improve the management of GL of frequently requested quantitative measurement procedures in clinical chemistry. Thus, the focus of these recommendations is on the distinction between reference interval limits and clinical decision limits as well as the determination and verification of reference interval limits. Indirect approaches are highlighted, as they enable routine laboratories with a broad analytical spectrum but limited resources to evaluate or to establish reference limits.

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Flexible scope for ISO 15189 accreditation: a guidance prepared by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group Accreditation and ISO/CEN standards (WG-A/ISO)

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2015-0257 ◽

2015 ◽

Vol 53 (8) ◽

Cited By ~ 8

Author(s):

Marc H.M. Thelen ◽

Florent J.L.A. Vanstapel ◽

Christos Kroupis ◽

Ines Vukasovic ◽

Guilaime Boursier ◽

...

Keyword(s):

Working Group ◽

Clinical Chemistry ◽

Laboratory Medicine ◽

Position Paper ◽

European Federation ◽

Medical Field ◽

Iso 15189 ◽

Medical Laboratories ◽

Flexible Scope ◽

Scientific Disciplines

AbstractThe recent revision of ISO15189 has further strengthened its position as the standard for accreditation for medical laboratories. Both for laboratories and their customers it is important that the scope of such accreditation is clear. Therefore the European co-operation for accreditation (EA) demands that the national bodies responsible for accreditation describe the scope of every laboratory accreditation in a way that leaves no room for doubt about the range of competence of the particular laboratories. According to EA recommendations scopes may be fixed, mentioning every single test that is part of the accreditation, or flexible, mentioning all combinations of medical field, examination type and materials for which the laboratory is competent. Up to now national accreditation bodies perpetuate use of fixed scopes, partly by inertia, partly out of fear that a too flexible scope may lead to over-valuation of the competence of laboratories, most countries only use fixed scopes. The EA however promotes use of flexible scopes, since this allows for more readily innovation, which contributes to quality in laboratory medicine. In this position paper, the Working Group Accreditation and ISO/CEN Standards belonging to the Quality and Regulation Committee of the EFLM recommends using an approach that has led to successful introduction of the flexible scope for ISO15189 accreditation as intended in EA-4/17 in The Netherlands. The approach is risk-based, discipline and competence-based, and focuses on defining a uniform terminology transferable across the borders of scientific disciplines, laboratories and countries.

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Optimizing the use of the “state-of-the-art” performance criteria

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2014-1201 ◽

2015 ◽

Vol 53 (6) ◽

Cited By ~ 3

Author(s):

Rainer Haeckel ◽

Werner Wosniok ◽

Thomas Streichert

Keyword(s):

State Of The Art ◽

Clinical Chemistry ◽

Reference Interval ◽

German Society ◽

Laboratory Medicine ◽

Biological Variation ◽

The State ◽

Analytical Performance ◽

Performance Criteria ◽

Performance Goals

AbstractThe organizers of the first EFLM Strategic Conference “Defining analytical performance goals” identified three models for defining analytical performance goals in laboratory medicine. Whereas the highest level of model 1 (outcome studies) is difficult to implement, the other levels are more or less based on subjective opinions of experts, with models 2 (based on biological variation) and 3 (defined by the state-of-the-art) being more objective. A working group of the German Society of Clinical Chemistry and Laboratory Medicine (DGKL) proposes a combination of models 2 and 3 to overcome some disadvantages inherent to both models. In the new model, the permissible imprecision is not defined as a constant proportion of biological variation but by a non-linear relationship between permissible analytical and biological variation. Furthermore, the permissible imprecision is referred to the target quantity value. The biological variation is derived from the reference interval, if appropriate, after logarithmic transformation of the reference limits.

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The zlog value as a basis for the standardization of laboratory results

LaboratoriumsMedizin ◽

10.1515/labmed-2017-0135 ◽

2017 ◽

Vol 41 (1) ◽

Author(s):

Georg Hoffmann ◽

Frank Klawonn ◽

Ralf Lichtinghagen ◽

Matthias Orth

Keyword(s):

Clinical Chemistry ◽

Standard Procedure ◽

Inverse Function ◽

Real Data ◽

Reference Interval ◽

Reference Population ◽

German Society ◽

Health Law ◽

Original Result ◽

Laboratory Results

AbstractBackground:With regard to the German E-Health Law of 2016, the German Society for Clinical Chemistry and Laboratory Medicine (DGKL) has been invited to develop a standard procedure for the storage and transmission of laboratory results. We suggest the commonly used z-transformation.Methods:This method evaluates by how many standard deviations (SDs) a given result deviates from the mean of the respective reference population. We confirm with real data that laboratory results of healthy individuals can be adjusted to a normal distribution by logarithmic transformation.Results:Thus, knowing the lower and upper reference limits LL and UL, one can transform any result x into a zlog value using the following equation:$\eqalign{ {\rm{zlog}} = & {\rm{(log(x)}}-{\rm{(log(LL)}} + {\rm{log(UL))/2)\cdot3}}{\rm{.92/(log(UL)}} \cr -{\bf{ }}{\rm{log(LL))}} \cr} $The result can easily be interpreted, as its reference interval (RI) is –1.96 to +1.96 by default, and very low or high results yield zlog values around –5 and +5, respectively. For intuitive data presentation, the zlog values may be transformed into a continuous color scale, e.g. from blue via white to orange.Using the inverse function, any zlog value can then be translated into the theoretical result of an analytical method with another RI:(1)$${\rm{x}} = {\rm{L}}{{\rm{L}}^{0.5 - {\rm{zlog}}/3.92}} \cdot {\rm{U}}{{\rm{L}}^{0.5 + {\rm{zlog}}/3.92}}$$Conclusions:Our standardization proposal can easily be put into practice and may effectively contribute to data quality and patient safety in the frame of the German E-health law. We suggest for the future that laboratories should provide the zlog value in addition to the original result, and that the data transmission protocols (e.g. HL7, LDT) should contain a special field for this additional value.

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Establishment of Reference Intervals for Alkaline Phosphatase in Pakistani Children Using a Data Mining Approach

Laboratory Medicine ◽

10.1093/labmed/lmz096 ◽

2019 ◽

Vol 51 (5) ◽

pp. 484-490 ◽

Cited By ~ 1

Author(s):

Sibtain Ahmed ◽

Jakob Zierk ◽

Aysha Habib Khan

Keyword(s):

Data Mining ◽

Alkaline Phosphatase ◽

Clinical Decision Making ◽

Clinical Chemistry ◽

Age Groups ◽

Clinical Decision ◽

German Society ◽

Reference Intervals ◽

Photometric Method ◽

Data Mining Approach

Abstract Objective To establish reference intervals (RIs) for alkaline phosphatase (ALP) levels in Pakistani children using an indirect data mining approach. Methods ALP levels analyzed on a Siemens Advia 1800 analyzer using the International Federation of Clinical Chemistry’s photometric method for both inpatients and outpatients aged 1 to 17 years between January 2013 and December 2017, including patients from intensive care units and specialty units, were retrieved. RIs were calculated using a previously validated indirect algorithm developed by the German Society of Clinical Chemistry and Laboratory Medicine’s Working Group on Guide Limits. Results From a total of 108,845 results, after the exclusion of patients with multiple specimens, RIs were calculated for 24,628 males and 18,083 females with stratification into fine-grained age groups. These RIs demonstrate the complex age- and sex-related ALP dynamics occurring during physiological development. Conclusion The population-specific RIs serve to allow an accurate understanding of the fluctuations in analyte activity with increasing age and to support clinical decision making.

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CE lebel and harmonisation of quality systems in medical laboratories

Jugoslovenska medicinska biohemija ◽

10.2298/jmh0401077m ◽

2004 ◽

Vol 23 (1) ◽

pp. 77-83

Author(s):

Nada Majkic-Singh

Keyword(s):

European Union ◽

Quality Management ◽

Quality Management System ◽

Clinical Chemistry ◽

Common Interest ◽

Medical Laboratory ◽

Total Quality ◽

Quality Systems ◽

Laboratory Practice ◽

Medical Laboratories

During the past ten years many activities have taken place in medical laboratories to harmonized the quality systems and accreditation activates. At that time, different approaches were followed in European countries concerning the demands for a quality system in a medical laboratory, and for the choice between certification or accreditation. Also, the working group on accreditation, of the European Communities Confederation of Clinical Chemistry (EC4) with as official name WG on Harmonization of Quality Systems and Accreditation was formed. From the start, the European Diagnostic Manufacturers Association (EDMA) was invited to participate, because harmonisation of quality systems and accreditation is of common interest. A crucial point in the quality revolution in medical laboratories is broad-based awareness of total quality management throughout the diagnostic business from manufacturers to laboratories to physicians and patients. In fact, the quality of laboratory tests largely depends on the products supplied (industry) and on quality management (laboratory management). Manufacturers recognize that accreditation gives high value to medical laboratories. However, while clinical laboratory practice is the responsibility of laboratory professionals, the in vitro diagnostics industry has a major role to play as the supplier of high quality goods and services, as training, scientific services, etc. On the other hand, the IVD industry is directly affected by accreditation schemes, and by the changes in laboratory practice and requirements that they initiate. The IVD Directive is a new example of legislative regulation that obliges the manufacturer (those who are not ISO 9000) to implement a quality management system. At the same time, the IVD Directive includes validation of products by competent laboratories, for ?sensitive? products. In fact, clinical laboratories should be assisted by manufacturers that provide reliable documentation, standard information for use, calibration procedure, performance checks and guide for preventive maintenance. The IVD Directive (EC 98/79) is released on December 1998, it is effective since June 2000 and final implementation is obliged from December 2003. IVDD shall ensure that only one safe and effective products will be sold in the European Union (EU), and just a single product approval is required to sell the products throughout the entire European Union. Official mark for products in conformity with the IVD Directive is CE label.

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Application of the TML method to big data analytics and reference interval harmonization

LaboratoriumsMedizin ◽

10.1515/labmed-2020-0133 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Mary Kathryn Bohn ◽

Khosrow Adeli

Keyword(s):

Clinical Chemistry ◽

A Priori ◽

Big Data Analytics ◽

Reference Interval ◽

German Society ◽

Reference Intervals ◽

Indirect Methods ◽

Advantages And Disadvantages ◽

Result Interpretation ◽

Indirect Reference

Abstract Significant variation in reported reference intervals across healthcare centers and networks for many well-standardized laboratory tests continues to exist, negatively impacting patient outcomes by increasing the risk of inappropriate and inconsistent test result interpretation. Reference interval harmonization has been limited by challenges associated with direct reference interval establishment as well as hesitancies to apply currently available indirect methodologies. The Truncated Maximum Likelihood (TML) method for indirect reference interval establishment developed by the German Society of Clinical Chemistry and Laboratory Medicine (DGKL) presents unique clinical and statistical advantages compared to traditional indirect methods (Hoffmann and Bhattacharya), increasing the feasibility of developing indirect reference intervals that are comparable to those determined using a direct a priori approach based on healthy reference populations. Here, we review the application of indirect methods, particularly the TML method, to reference interval harmonization and discuss their associated advantages and disadvantages. We also describe the CSCC Reference Interval Harmonization Working Group’s experience with the application of the TML method in harmonization of adult reference intervals in Canada.

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The Haemolytic, Icteric and Lipemic Sample Recommendations Regarding their Recognition and Prevention of Clinically Relevant Interferences. Recommendations of the Working Group on Preanalytical Variables of the German Society for Clinical Chemistry and the German Society for Laboratory Medicine

LaboratoriumsMedizin ◽

10.1515/labm.2000.24.8.357 ◽

2000 ◽

Vol 24 (8) ◽

pp. 357-364 ◽

Cited By ~ 4

Author(s):

W.G. Guder ◽

F. da Fonseca-Wollheim ◽

W. Heil ◽

Y. M. Schmitt ◽

G. Töpfer ◽

...

Keyword(s):

Working Group ◽

Clinical Chemistry ◽

German Society ◽

Laboratory Medicine

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Improvement of therapeutic safety through standardized plasma calibration of blood glucose test systems at the point-of-care1/ Statement of the POCT Working Group of the German Society for Clinical Chemistry and Laboratory Medicine (DGKL)

LaboratoriumsMedizin ◽

10.1515/jlm.2009.058et ◽

2009 ◽

Vol 33 (6) ◽

pp. ---

Author(s):

For the POCT Working Group: Theodor Koschinsky ◽

Ralf Junker ◽

Peter B. Luppa ◽

Harald Schlebusch

Keyword(s):

Blood Glucose ◽

Working Group ◽

Clinical Chemistry ◽

German Society ◽

Laboratory Medicine ◽

Test Systems ◽

Blood Glucose Test ◽

Glucose Test ◽

Therapeutic Safety

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Comparison of regression for blood ALP levels using methods of the Japan Society of Clinical Chemistry and the International Federation of Clinical Chemistry and Laboratory Medicine in bovine, canine, feline, and human testing

PLoS ONE ◽

10.1371/journal.pone.0253396 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0253396

Author(s):

Akihisa Hata ◽

Noboru Fujitani ◽

Masahiro Takeshita ◽

Chie Tanaka ◽

Noriko Matsuda ◽

...

Keyword(s):

Veterinary Medicine ◽

Clinical Laboratory ◽

Clinical Chemistry ◽

Animal Health ◽

Laboratory Medicine ◽

International Federation ◽

Medical Laboratory ◽

Japan Society ◽

Medical Laboratories ◽

Laboratory Technology

Livestock and companion animal health have a direct impact on human health. Research on clinical laboratory technology for veterinary medicine is as important as that on human laboratory technology. Reagents and analysis equipment for human medical laboratory tests are often used in veterinary medicine. Medical laboratories in Japan utilize the Japan Society of Clinical Chemistry (JSCC) method for blood alkaline phosphatase (ALP) analysis. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) method is used worldwide for ALP catalytic concentration measurement. When the IFCC method is used, human blood ALP activity is approximately one-third of the JSCC method’s activity. The JSCC method for ALP measurement was switched to the IFCC method in medical laboratories in Japan in April 2020 for global standardization purpose. It is uncertain whether conventional JSCC method reagents will continue to be supplied. In veterinary medicine, the relationship between the JSCC and IFCC methods in terms of ALP measurement is almost unclear. This study investigated the regression between JSCC and IFCC methods measuring ALP in bovine, canine, feline, and human. The regression formulas for bovine, canine, feline, and human ALP values using the conventional JSCC (x) and IFCC (y) methods are y = 0.379x + 0.124, y = 0.289x + 8.291, y = 0.358x + 0.432, and y = 0.337x + 2.959, respectively. These results suggested that the IFCC method measurement could be estimated by approximately one-third of the JSCC method measurement in animal species such as bovine, canine, and feline. By applying the conversion factors proposed in this study, a very good correlation could be obtained between the two methods for each animal.

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